Implants are utilized in modern medical technology in a variety of embodiments, including for example implants that perform a support function, such as stents, implants that perform a control function e.g. electrodes and implants that perform a measurement or monitoring function (e.g. sensors). Implants can be used for example to support vessels, hollow organs, and ductal systems (endovascular implants, e.g. stents), to fasten and temporarily fix tissue implants and tissue transplants in position, as well as for orthopedic purposes such as pin, plate, or screw and others. The stent is a form of an implant that is used particularly frequently.
Stent implantation has become established as one of the most effective therapeutic measures for treating vascular disease. Stents are used to provide support in a patient's hollow organs. To this end, stents of a conventional design have a filigree support structure composed of metallic struts; the support structure is initially present in a compressed form for insertion into the body, and is expanded at the application site. One of the main applications of stents of this type is to permanently or temporarily widen and hold open vasoconstrictions, in particular constrictions (stenoses) of the coronary arteries. In addition, aneurysm stents are known, for example, which are used to support damaged vascular walls.
Many stents include a circumferential wall having a support force that suffices to hold the constricted vessel open to the desired extent; many stents also include a tubular base body through which blood continues to flow without restriction. The circumferential wall is typically formed by a latticed support structure that enables the stent to be inserted, in a compressed state having a small outer diameter, until it reaches the constriction in the particular vessel to be treated, and to be expanded there, for example using a balloon catheter, to the extent that the vessel finally has the desired, increased inner diameter.
The implant, in particular the stent, has a base body composed of an implant material. An implant material is a nonliving material that is used for a medical application and interacts with biological systems. A prerequisite for the use of a material as an implant material that comes in contact with the body environment when used as intended is its biocompatibility.
“Biocompatibility” refers to the capability of a material to evoke an appropriate tissue response in a specific application. This includes an adaptation of the chemical, physical, biological, and morphological surface properties of an implant to the recipient tissue, with the objective of achieving a clinically desired interaction. The biocompatibility of the implant material is furthermore dependent on the time sequence of the response of the biosystem in which the implant is placed. For example, irritations and inflammations, which can cause tissue changes, occur over the relative short term. Biological systems therefore respond differently depending on the properties of the implant material. Depending on the response of the biosystem, implant materials can be subdivided into bioactive, bioinert, and degradable/resorbable materials.
Implant materials include polymers, metallic materials, and ceramic materials (as coating, for example). Biocompatible metals and metal alloys for permanent implants can contain, for example, stainless steels (e.g. 316L), cobalt-based alloys (e.g. CoCrMo casting alloys, CoCrMo forging alloys, CoCrWNi forging alloys, and CoCrNiMo forging alloys), pure titanium and titanium alloys (e.g. CP titanium, TiAl6V4 or TiAl6Nb7), and gold alloys. In the field of biocorrodible stents, the use of magnesium or pure iron and biocorrodible base alloys of the elements magnesium, iron, zinc, molybdenum, and tungsten is proposed.
A biological response to polymeric, ceramic, or metallic implant materials depends on the concentration, duration of exposure, and type of supply. The presence of an implant material often evokes inflammatory responses which can be triggered by mechanical irritations, chemical substances, or metabolites. The inflammatory process is typically accompanied by the immigration of neutrophil granulocytes and monocytes through the vascular walls, the immigration of lymphocyte effector cells with the formation of specific antibodies to the inflammatory stimulus, activation of the complement system with the release of complement factors which act as mediators, and, ultimately, activation of blood coagulation. An immunological response is usually closely associated with the inflammatory response and can lead to sensitization and the development of allergies. Known metallic allergens include nickel, chromium, and cobalt which are also used in many surgical implants as alloying constituents. A problem associated with the implantation of a stent in a blood vessel is in-stent restenosis due to excessive neointimal growth caused by a strong proliferation of arterial smooth muscle cells and a chronic inflammatory response.
It is known that a greater level of biocompatibility can be achieved by coating implant materials with particularly tissue-compatible materials. These materials are usually organic or synthetic-polymeric in nature and are partially of natural origin. Further strategies for preventing restenosis focus on inhibiting proliferation using medication e.g. treatment using cytostatic agents. The active ingredients can be provided e.g. on the implant surface in the form of a coating that releases an active ingredient.
It is furthermore known that the RGD triad (Arg-Gly-Asp) serves many integrins as a primary recognition site for proteins of the extracellular matrix. Peptides that contain this sequence can therefore mimic the ligands of these integrins and bind thereto.
Due to the fact that RGD peptides are selective antagonists for integrins, their medical relevance—or the medical relevance of peptidomimetics derived therefrom—is the subject of research.